Heretofore, compounds having an angiotensin II receptor antagonistic activity and a peroxisome proliferator-activated receptor γ agonistic activity have been reported, for example, in WO2008/062905, WO2008/143262 and the like.
WO 2008/062905 describes a compound of the following formula
wherein R1 is (1) an oxo group; (2) a thioxo group; (3) a group represented by the formula: ═N—R; R is(i) an optionally substituted C1-C6 alkyl group or the like; a group represented by the formula:
wherein R2 is a group represented by the formula:
wherein R6 is a group represented by the formula:
wherein Z is O or S(O)n (n is an integer of 0 to 2), andY is an optionally substituted C1-C4 alkylene group or the like;R3 and R4 are each independently(1) a hydrogen,(2) an optionally substituted C1-C6 alkyl group or the like, andR5 is(1) a hydrogen,(2) an optionally substituted C1-C6 alkyl group,(3) an optionally substituted C2-C6 alkenyl group,(4) an optionally substituted cyclic group,(5) a group represented by the formula: —CO—R8wherein R8 is an optionally substituted C1-C6 alkyl group or an optionally substituted cyclic group, or(6) a group represented by the formula: —O—R8′wherein R8′ is an optionally substituted C1-C6 alkyl group or an optionally substituted cyclic group, or a salt thereof.
WO2008/143262 describes a compound represented by the formula (I):
wherein a group represented by the formula:
is a group represented by the formula (a):
wherein,R1 is a hydrogen atom, a (C1-C6)alkyl group optionally having substituent(s) or the like;X is a group represented by the formula: CO—X1, S(O)n-X1 or (R2)C═C(R3) wherein X1 is a group represented by the formula: N(R4) or (R5)C(R6) wherein R4 and R5 are each a hydrogen atom, a (C1-C6)alkyl group optionally having substituent(s), or a cyclic group optionally having substituent(s), and R6 is a (C1-C6)alkyl group optionally having substituent(s), R2 is a hydrogen atom, a (C1-C6)alkyl group optionally having substituent(s) or the like, R3 is a hydrogen atom, a (C1-C6)alkyl group optionally having substituent(s), or a cyclic group optionally having substituent(s), and n is 1 or 2;Y is a nitrogen atom or a group represented by the formula: C(R7) wherein R7 is a hydrogen atom, or a (C1-C6)alkyl group optionally having substituent(s); andm is 0 or 1, providedwhen m is 1, R3 or R4 is optionally bonded to a carbon atom, which is adjacent to the nitrogen atom or a carbon atom bonded thereto, to form a ring,R is a group represented by the formula:
wherein,Ra is a (C1-C6)alkylene group optionally having substituent(s) or the like; Rb is a group represented by the formula:
wherein W is an oxygen atom or a sulfur atom, which optionally has substituent(s), wherein the biphenyl group optionally further having substituent(s), or a salt thereof and the like.
In addition, US2004/127443 describes a method for treating or preventing an inflammatory or metabolic disorder in a mammal by administering, to the mammal in need thereof, a therapeutically effective amount of a compound sufficient to (a) at least partially activate peroxisome proliferator activated receptors (PPARs) and (b) at least partially inhibit, antagonize or block an activity of angiotensin II type 1 receptors.
WO1995/26724 describes a method of improving insulin resistance using an angiotensin II receptor antagonist and a method of improving insulin sensitivity accompanying a treatment of hypertension.
WO2007/053406, WO2007/051007, WO2007/013078, WO2006/000564, WO2005/288272, WO2005/020984, WO2004/053903, WO1996/40258, WO1996/40257, WO1996/40256, WO1996/40255, WO2009/137465, WO2009/118292, WO2009/039069, US2009/0012052 and WO2008/060899 describe the compound of the following formula and that the compound has angiotensin II antagonistic activity and hypotensive activity and is useful as therapeutic agents for circulatory disease such as hypertension, cardiac diseases, cerebral apoplexy and the like.

WO1994/17067 describes compounds represented by the following formulas, and that the compounds have angiotensin II antagonistic activity and hypotensive activity and are useful as therapeutic agents for circulatory disease such as hypertension, cardiac diseases, cerebral apoplexy and the like.

U.S. Pat. No. 5,389,632 describes a compound represented by the following formula
wherein one of R1 and R2 is C1-6 alkyl, —(CH2)pOR (p is an integer of 1 to 6, and R is C1-6 alkyl or benzyl) and the other of R1 and R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, OR4, SR4, NR5R6 or NH(CH2)n—NR5R6 (wherein R4 is a hydrogen atom, C1-6 alkyl, C3-7 cycloalkyl, (CH2)m—COOR′ or (CH2)m—O—R′ (wherein m is an integer of 1 to 4, and R′ is a hydrogen atom or C1-6 alkyl), R5 and R6 are the same or different and each is a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl, or R5 and R6 form, together with the nitrogen atom bonded to the both, a hetero ring selected from morpholine, pyrrolidine and piperidine, and n is an integer of 1 to 4), X at the 2-position or the 3-position of pyrazolo[1,5-a]pyrimidine is a hydrogen atom, C1-6 alkyl, hydroxyl or COOR′ (R′ is as defined above), and R3 is the formula
wherein Z is CH or a nitrogen atom, Z′ is a sulfur atom or an oxygen atom, R11 is a hydrogen atom or a halogen atom, and R12 is tetrazolyl, CN, COOH or CONH2,or a salt thereof, and describes that the compound has angiotensin II antagonistic activity and hypotensive activity, and is useful as therapeutic agent for circulatory diseases such as hypertension, cardiac diseases, cerebral apoplexy and the like.
U.S. Pat. No. 5,387,747 describes a compound represented by the following formula
wherein one of R1 and R2 is C1-6 alkyl, —(CH2)pOR or —(CH2)pOH (p is an integer of 1 to 6, and R is C1-6 alkyl or benzyl) and the other of R1 and R2 is a hydrogen atom, a halogen atom, C1-6 alkyl, N3, OR4, SR4, NR5R6 or NH(CH2)n—NR5R6 (wherein R4 is a hydrogen atom, C1-6 alkyl, C3-7 cycloalkyl, (CH2)n—COOR′ or (CH2)m—O—R′ (wherein m is an integer of 1 to 4, and R′ is a hydrogen atom or C1-6 alkyl), R5 and R6 are the same or different and each is a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl, or R5 and R6 form, together with the nitrogen atom bonded thereto, a hetero ring selected from morpholine, pyrrolidine and piperidine, and n is an integer of 1 to 4), X and Y are the same or different and when one of them is a nitrogen atom, the other is C—R7 (wherein R7 is a hydrogen atom, C1-6 alkyl, C3-7 cycloalkyl, (CH2)n′OH (wherein n′ is an integer of 0 to 4), SR′ (R′ is as defined above), NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl)), and R3 is the formula
wherein Z is CH or a nitrogen atom, Z′ is a sulfur atom or an oxygen atom, R11 is a hydrogen atom or a halogen atom, and R12 is tetrazolyl, CN, COOH or CONH2),or a salt thereof, and describes that the compound has angiotensin II antagonistic activity and hypotensive activity, and is useful as therapeutic agent for circulatory diseases such as hypertension, cardiac diseases, cerebral apoplexy and the like.
U.S. Pat. No. 5,231,094 describes a compound represented by the formula
wherein one of R1 and R2 is C1-6 alkyl and the other is a hydrogen atom, a halogen atom, OR4, SR4, NR5R6 or NR4(CH2)n—NR5R6 (wherein R4 is a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl, R5 and R6 are the same or different and each is a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl, or R5 and R6 form, together with the nitrogen atom bonded to the both, a hetero ring selected from morpholine, pyrrolidine, piperazine, piperidine and immidazolidine, and n is an integer of 1 to 4, two of X, Y and Z are nitrogen atoms, and the other is C—R7 (wherein R2 is a hydrogen atom or C1-6 alkyl), and R3 is tetrazolyl,or a salt thereof, and describes that the compound has angiotensin II antagonistic activity and hypotensive activity, and is useful as a therapeutic agent for circulatory diseases such as hypertension, cardiac diseases, cerebral apoplexy and the like.